3-187744934-C-G

Variant names:

• chr3-187744934-C-G
• rs80031434
• NM_001706.5:c.-50+476G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001706.5(BCL6):​c.-50+476G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,214 control chromosomes in the GnomAD database, including 825 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (825 hom., cov: 32)
• Consequence: BCL6 NM_001706.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98
• Publications: 3 publications found

Genes affected

BCL6 (HGNC:1001): (BCL6 transcription repressor) The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal POZ domain. This protein acts as a sequence-specific repressor of transcription, and has been shown to modulate the transcription of STAT-dependent IL-4 responses of B cells. This protein can interact with a variety of POZ-containing proteins that function as transcription corepressors. This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL. Alternatively spliced transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

BCL6-AS1 (HGNC:):

BCL6-AS1 (HGNC:51843): (BCL6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001706.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	NM_001706.5	MANE Select	c.-50+476G>C		intron	N/A	NP_001697.2
	BCL6	NM_001134738.2		c.-50+476G>C		intron	N/A	NP_001128210.1
	BCL6-AS1	NR_173091.1		n.377-310C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL6	ENST00000406870.7	TSL:1 MANE Select	c.-50+476G>C		intron	N/A	ENSP00000384371.2	P41182-1
	BCL6	ENST00000621333.4	TSL:5	c.-50+476G>C		intron	N/A	ENSP00000479784.1	P41182-2
	BCL6	ENST00000470319.1	TSL:4	n.63+476G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15169 AN: 152094 Hom.: 821 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0999 AC: 15199 AN: 152214 Hom.: 825 Cov.: 32 AF XY: 0.103 AC XY: 7651 AN XY: 74410

African (AFR) AF: 0.0629 AC: 2611 AN: 41530

American (AMR) AF: 0.102 AC: 1554 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5148

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1543 AN: 10608

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7429 AN: 68010

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.0498 Hom.: 54

Bravo AF: 0.0974

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs80031434; hg19: chr3-187462722;